lignans and chrysophanic-acid

Intestinal obstruction (IO) is a kind of acute abdomen with high morbidity and mortality. Patients suffer from poor quality of life and tremendous financial pressure. Da-Cheng-Qi decoction (DCQD), a classical purgation prescription, has clinically been proven to be an effective treatment for IO.. Network pharmacology integrated with bioactive equivalence assessment was used to discover the quality marker (Q-marker) of DCQD against IO.. As there is hardly any targets recorded in database, thus the collection of IO targets was conducted by searching those of alternative diseases which have similar pathological symptoms with IO. In order to improve the reliability of the obtained targets, IO metabolomics data was introduced. Active compounds combination (ACC) was focused as potential Q-markers via component-target network analysis and function query from the identified components corresponding to the common targets. Bioequivalence between ACC and DCQD was assessed from the aspects of intestine motility (somatostatin secretion), inflammation (IL-6 secretion) and injury (wound healing assay) in vitro and was further validated in ileus rat model. PPI network analysis of core targets followed by gene pedigree classification and experimental validation confirmed the potential intervention pathway.. A combination of 11 ingredients, including emodin, physcion, aloe-emodin, rhein, chrysophanol, gallic acid, magnolol, honokiol, naringenin, tangeretin, and nobiletin was finally confirmed bioequivalence with DQCD to some extent and could serve as Q-markers for DCQD to attenuate IO. PI3K/AKT was verified as a possible affected pathway that DCQD exerted the effectiveness against IO.. For the disease with few recorded targets, searching those of alternative diseases which have similar pathological symptoms could be a feasible and effective approach. The proposed network pharmacology integrated bioactive equivalence evaluation paradigm is efficient to discover Q-marker of herbal formulae.

Topics: Algorithms; Animals; Anthraquinones; Biomarkers, Pharmacological; Biphenyl Compounds; Data Mining; Drugs, Chinese Herbal; Flavanones; HT29 Cells; Humans; Intestinal Obstruction; Lignans; Male; Phosphatidylinositol 3-Kinases; Rats, Sprague-Dawley; Reproducibility of Results; Therapeutic Equivalency

To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis.. Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated.. The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (. DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Topics: Acute Disease; Alanine Transaminase; Animals; Anthraquinones; Aspartate Aminotransferases; Biphenyl Compounds; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Emodin; Flavanones; Hesperidin; Inflammation; Lignans; Liver; Male; Pancreatitis; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Masiningan is a traditional medicine consisting of six crude drugs that have been used for treating constipation and diabetes mellitus in both Japan and China. Masiningan has been reported to have significant PTP1B inhibitory activity and to affect cells in the insulin-signaling pathway. The aim of the present study is to identify the PTP1B inhibitory compounds in Masiningan.. Bioactivity peaks were identified by analytical HPLC profiling and PTP1B inhibitory activity profiling of sub-fractions from Masiningan extract. The bioactive compounds were isolated by tracking two identified bioactive peaks, and the chemical structures were determined by spectroscopic analyses. The bioactive compounds were further investigated for their inhibitory effect against PTP1B by enzymatic kinetic analysis, molecular docking simulation, inhibitory selectivity against other PTPs, and cellular activity in the insulin signal transduction pathway.. From Masiningan, magnolol (1) and chrysophanol (2) were isolated as compounds that exhibited significant dose-dependent inhibitory activities against PTP1B, with IC50 values of 24.6 and 12.3μM, respectively. Kinetic analysis revealed that 1 is a non-competitive and that 2 is a competitive PTP1B inhibitor. In the molecular docking simulation, compound 2 was stably positioned in the active pocket of PTP1B, and the CDOCKER energy was calculated to be 24.3411kcal/mol. Both compounds demonstrated remarkably high selectivity against four PTPs and revealed cellular activity against the insulin signal transduction pathway.. Magnolol (1) and chrysophanol (2) were identified as the principle PTP1B inhibitory active compounds in Masiningan, and their actions were investigated in detail. These findings demonstrated the effectiveness of Masiningan on diabetes mellitus through the inhibition of PTP1B at a molecular level as well as the potential of magnolol (1) and chrysophanol (2) as lead compounds in future anti-diabetes drug development.

Topics: Anthraquinones; Biphenyl Compounds; Catalytic Domain; Humans; Japan; Kinetics; Lignans; Medicine, Kampo; Models, Molecular; Molecular Structure; Protein Conformation; Protein Tyrosine Phosphatase, Non-Receptor Type 1

To investigate the effect of prescription compatibility on the pharmacokinetics of components from Dachengqi Decoction (DCQD, ) in rats.. Twenty-four male rats were randomly and equally divided into the DCQD group, Dahuang (Radix et Rhizoma Rhei, Polygonaceae) group, Houpo (Magnolia officinalis Rehd., Magnoliaceae) group, and Zhishi (Fructus Aurantii Immaturus, Rutaceae) group. The blood samples were collected before dosing and subsequently at 10, 15, 20, 30, 45 min, 1, 2, 4, 8, and 12 h following gavage. The levels of aloe-emodin, rhein, emodin, chrysophanol, honokiol, magnolol, hesperidin, and naringin in rat serum were quantified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic study.. The area under the curve (AUC), mean retention time (MRT), the peak concentration (C(max)) of aloe-emodin, rhein, emodin, and chrysophanol in the DCQD group were significantly different compared with the Dahuang group (P <0.05, respectively). The mean plasma concentration, C(max), and the absorption of Dahuang's component in the DCQD group were obviously lower at each time point than those in the Dahuang group, while the elimination process of Dahuang's component was obviously delayed (P <0.05). Half-lives of aloe-emodin, chrysophanol, and rhein were also extended in the DCQD group (P <0.05, respectively). In the DCQD group, the mean plasma concentration, AUC, C(max) and absorption of honokiol, and magnolol were significantly lower (P <0.01, respectively) at each time point than those in the Houpo group, while the drug distribution half-life time (T(1/2α)), the drug eliminated half-life time (T(1/2β)), MRT, and time of peak concentration (T(max)) were significantly delayed (P <0.05, respectively). Pharmacokinetic parameters of hesperidin and naringin in the Zhishi group were not significantly different as compared with the DCQD group (P >0.05, respectively), while the MRT of naringin was significantly longer.. The compatibility in Chinese medicine could affect the drug's pharmacokinetics in DCQD, which proves that the prescription compatibility principle of Chinese medicine formulations has its own pharmacokinetic basis.

Topics: Administration, Oral; Animals; Anthraquinones; Biphenyl Compounds; Drug Incompatibility; Emodin; Flavanones; Hesperidin; Lignans; Male; Plant Extracts; Rats; Rats, Sprague-Dawley

To investigate the effect of severe acute pancreatitis (SAP) on pharmacokinetics of Da-Cheng-Qi Decoction (DCQD) components in rats.. Rats were divided into SAP group and sham-operation group as a control group (n = 6). Rhein, chrysophanol, rheochrysidin, magnolol, hesperidin and naringin in DCQD were quantified in rat serum by high performance liquid chromatography tandem mass spectrometry for studying their pharmacokinetics.. Early absorption of each DCQD component was tended to degrade in SAP group after treatment with DCQD by gavage. The C(max) (chrysophanol, P = 0.0059; rheochrysidin, P = 0.0288; magnolol, P = 0.0487; hesperidin, P = 0.0277; naringin, P = 0.0023) and AUC (rhein, P = 0.0186; chrysophanol, P = 0.0013; magnolol, P = 0.001; hesperidin, P = 0.0081; naringin, P = 0.0272) of DCQD component were obviously lower in SAP group than in control group. The T(1/2alpha) of chrysophanol and rheochrysidin (P = 0.0467 and 0.0005, respectively) and T(max) of chrysophanol and rheochrysidin (P = 0.0101 and 0.0037, respectively) lasted longer in SAP group than in control group.. SAP can significantly impact the absorption of DCQD components in rats and their pharmacokinetic parameters.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Enzyme Inhibitors; Flavanones; Glucosides; Hesperidin; Humans; Lignans; Male; Molecular Structure; Mutagens; Pancreatitis, Acute Necrotizing; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley

To study the chemical constituents and volatile oil of Xiaochengqi decoction.. The constituents in decoction were separated by means of column chromatography and their structures were identified by spectral data and compared with literature data. As well as the volatile oil of Xiaochengqi Fang were analyzed and identified by GC-MS.. Eleven compounds were isolated and identified as chrysophanol (1), physcion (2), magnolol (3), beta-sitosterol (4), sitosterol trans-cinnamic acid (5), emodin (6), aloe emodin (7), rhein (8), gallic acid (9), chrysophanol-8-O-beta-D-glucopyranoside (10), aurantiamarin (11). The volatile oils extracted with steam distillation from Xiaochengqi were identified 67 components, and the main components are including.. All of the eleven compounds were isolated from Xiaochengqi decoction for the first time and the study on their activities in Chinese prescription is being carried out. D-limonene (42.61%), p-cymene (16.43%), and 8-terpinene (14.46%).

Topics: Anthraquinones; Biphenyl Compounds; Cinnamates; Cyclohexenes; Cymenes; Drugs, Chinese Herbal; Emodin; Gallic Acid; Gas Chromatography-Mass Spectrometry; Lignans; Limonene; Monoterpenes; Oils, Volatile; Sitosterols; Terpenes

Extracts of the Egyptian marine actinomycete, Nocardia sp. ALAA 2000, were found to be highly bioactive. It was isolated from the marine red alga Laurenica spectabilis collected off the Ras-Gharib coast of the Red Sea, Egypt. According to detailed identification studies, the strain was classified as a member of the genus Nocardia. The cultivation and chemical analysis of this species yielded four structurally related compounds namely, chrysophanol 8-methyl ether (1), asphodelin; 4,7'-bichrysophanol (2) and justicidin B (3), in addition to a novel bioactive compound ayamycin; 1,1-dichloro-4-ethyl-5-(4-nitro-phenyl)-hexan-2-one (4) which is unique in contain both chlorination and a rarely observed nitro group. The compounds were isolated by a series of chromatographic steps and their structures of 1approximately 3 secured by detailed spectroscopic analysis of the MS and NMR data whereas that of 4 was elucidated by single crystal X-ray diffraction studies. These compounds displayed different potent antimicrobial activity against both Gram-positive and Gram-negative bacteria as well as fungi with MIC ranging from 0.1 to 10 microg/ml.

Topics: Anthraquinones; Anti-Bacterial Agents; Antifungal Agents; Chromatography; Coumarins; Crystallography, X-Ray; Dioxolanes; Egypt; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Laurencia; Lignans; Microbial Sensitivity Tests; Molecular Structure; Nocardia